A[beta] ve Tau birikiminin genetik sebepleri ile ilgili en guclu genetik veriler, amiloid precursor protein (APP), presenilin-1
(PSEN1) veya PSEN-2'deki mutasyonlarla ilgili calismalarindan elde edilmistir.
They are individually regulated by APP , presenilin-1
( PS1 ), PS2 , and tau protein genes.
Li et al., "A presenilin-1
mutation renders neurons vulnerable to isoflurane toxicity," Anesthesia and Analgesia, vol.
Li, "Curcumin mediates presenilin-1
activity to reduce [beta]-amyloid production in a model of Alzheimer's disease," Pharmacological Reports, vol.
The 5xFAD mouse is a transgenic model of AD carrying five mutations associated with early onset familial Alzheimer's disease (FAD): the K670N/M671L (Swedish), I716V (Florida), and V717I (London) mutations in human amyloid precursor protein (APP) and the M146L and L286V mutations in human presenilin-1
Gordon et al., "Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1
transgenes," Brain Research, vol.
Familial AD comprises <5% of cases and is associated with a distinct autosomal genetic mutation associated with the amyloid precursor protein (APP), presenilin-1
(PSEN-1), and presenilin-2 (PSEN-2) [5, 12-18].
Loss of function mutations in the gamma-secretase genes--including presenilin-1
, presenilin enhancer-2, and nicastrin--likely play a role (5, 15).
The brain glucose deficit isn't unique to the elderly, or even to patients with AD--it also occurs in those who have a family history of the disease, who carry the APOE4 allele, those with presenilin-1
mutations, and those with insulin resistance and diabetes.
In support of this hypothesis, it has been shown that genetic overexpression of amyloid precursor protein and presenilin-1
, or genetic deletion of Ear2, which promotes LC development [104, 105], both modestly impair hippocampal long-term potentiation and spatial memory.
Presenilins are transmembrane proteases that in humans are represented by two homologs, presenilin-1
(PS-1) and presenilin-2 (PS-2), encoded by two gens, PSEN1 and PSEN2, respectively .
Three dominant inherited mutations in the genes amyloid precursor protein (APP), presenilin-1
(PS1), and presenilin-2 (PS2), which increase the production of amyloid-beta (A[beta]) peptides, have been linked to EOAD [9, 10].